Liraglutide in the Treatment of Type 1 Diabetes Mellitus

Summary

Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases fasting, postprandial and the overall mean glucose concentrations. Aim 1.1: To compare the mean fasting, the mean weekly glucose and the standard deviation of weekly blood glucose concentrations as recorded by continuous glucose monitoring prior to and following 6 weeks and 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. In addition, the time spent at glucose concentrations \>150 and 200mg/dl and \<70 and \<40 mg/dl will also be compared. Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Glucose concentrations will be measured as areas under the curve for the data obtained from the meal challenge. Aim 1.3: To compare HbA1c levels(glycated hemoglobin) before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases postprandial glucagon concentrations and increases postprandial C-peptide concentrations. Aim 2.1: To compare fasting and postprandial glucagon and C-peptide concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric emptying. Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily.

Timeline

Start

2012-11-01

Primary completion

2014-04-01

Completion

2014-12-01

Publications

• Background Kuhadiya ND, Malik R, Bellini NJ, Patterson JL, Traina A, Makdissi A, Dandona P. Liraglutide as additional treatment to insulin in obese patients with type 1 diabetes mellitus. Endocr Pract. 2013 Nov-Dec;19(6):963-7. doi: 10.4158/EP13065.OR.
• Background Varanasi A, Bellini N, Rawal D, Vora M, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011 Jul;165(1):77-84. doi: 10.1530/EJE-11-0330. Epub 2011 Jun 6.
• Background Kielgast U, Asmar M, Madsbad S, Holst JJ. Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients. J Clin Endocrinol Metab. 2010 May;95(5):2492-6. doi: 10.1210/jc.2009-2440. Epub 2010 Mar 5.
• Background Rother KI, Spain LM, Wesley RA, Digon BJ 3rd, Baron A, Chen K, Nelson P, Dosch HM, Palmer JP, Brooks-Worrell B, Ring M, Harlan DM. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care. 2009 Dec;32(12):2251-7. doi: 10.2337/dc09-0773. Epub 2009 Oct 6.
• Background Ghanim H, Aljada A, Daoud N, Deopurkar R, Chaudhuri A, Dandona P. Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Diabetologia. 2007 Feb;50(2):278-85. doi: 10.1007/s00125-006-0508-9. Epub 2006 Dec 16.
• Background Wajchenberg BL, Feitosa AC, Rassi N, Lerario AC, Betti RT. Glycemia and cardiovascular disease in type 1 diabetes mellitus. Endocr Pract. 2008 Oct;14(7):912-23. doi: 10.4158/EP.14.7.912.
• Background Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007 Jan;29(1):139-53. doi: 10.1016/j.clinthera.2007.01.015.
• Background Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009 Nov;31(11):2472-88. doi: 10.1016/j.clinthera.2009.11.034.
• Background Varanasi A, Patel P, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P. Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors. Endocr Pract. 2012 Mar-Apr;18(2):140-5. doi: 10.4158/EP11169.OR.
• Background Varanasi A, Chaudhuri A, Dhindsa S, Arora A, Lohano T, Vora MR, Dandona P. Durability of effects of exenatide treatment on glycemic control, body weight, systolic blood pressure, C-reactive protein, and triglyceride concentrations. Endocr Pract. 2011 Mar-Apr;17(2):192-200. doi: 10.4158/EP10199.OR.
• Background Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010 Mar;23(3):334-9. doi: 10.1038/ajh.2009.245. Epub 2009 Dec 17.
• Background Lebovitz HE. Adjunct therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010 Jun;6(6):326-34. doi: 10.1038/nrendo.2010.49. Epub 2010 Apr 20.
• Kuhadiya ND, Dhindsa S, Ghanim H, Mehta A, Makdissi A, Batra M, Sandhu S, Hejna J, Green K, Bellini N, Yang M, Chaudhuri A, Dandona P. Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks. Diabetes Care. 2016 Jun;39(6):1027-35. doi: 10.2337/dc15-1136. Epub 2016 Apr 5.

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